HPI: 28 YO Caucasian Female with DM type I & h/o right ovarian tumor s/p resection in 2012 presents with 4 days of sore throat. Patient originally visited urgent care 4 days ago, given Keflex and sent home. In the interim, patient has worsening symptoms of sore throat and increasing tender cervical lymphadenopathy R > L. Endorses nausea without vomiting, and subjective fevers without measurement. Denies CP, palpitations, abdominal pain, urinary symptoms. Denies use of tobacco, alcohol, or drugs.

PMH:

• DM Type I s/p Insulin pump
• Right ovarian tumor s/p resection 2012
• Migraines
• Anxiety

PSH:

• Right Oophorectomy 2012

SHx:

• Denies tobacco, alcohol, or drug use.

Initial VS:

• BP 133/82, P 110, R 16, T 37.7, P 9/10, Sat 97% RA

PE:

• Non-toxic appearing. BL swollen tonsils R > L with erythema and exudates with necrotic lesion on right. Isolated right, tender cervical lymphadenopathy ~ 2 cm. Cardiopulmonary benign. Abdomen benign. Tachycardia, otherwise VSS.

DDX:

• Pharyngitis (Strep vs. Gonorrhea), Tonsillitis, PTA, URI

ED Course:

• 1 L NS, 1 g Rocephin IVP, Tylenol 1 g PO (for pain, patient denied stronger meds)
• CT Soft tissue neck for concern of PTA: No concerning signs of abscess noted in tonsillar region, however significant BL cervical and mandibular lymphadenopathy & BL tonsillar swelling
• Patient admitted to medicine for further workup and management of both infection and DM Type I

Labs:

• CBC normal
• CMP glucose 199, otherwise normal
• HCG negative
• Strep A PCR throat negative
• Mono screen negative
• Gonorrhea culture throat negative
• Culture throat: Group F Streptococcus Anginosus (S. milleri group)

Introduction:

Acute pharyngitis is a relatively common condition found in the ED accounting for 12 million ambulatory case visits or about 1-2% of all ambulatory case visits (Schappert 2008), many of which occur in the ED with the increasing frequency of patients having no primary care physician to turn to. It is imperative to be able to recognize and treat according to best practice guidelines with regards to antibiotic therapy. The most common organisms involved are viral & Group A streptococcus. There are many uncommon organisms that could be involved that should be considered if either the patient is not responding to standard therapy, or the suspected organisms are not found via standard tests. One of these very rare organisms is Group F Streptococcus Anginosus (S. milleri group previously). 

Group F Streptococcus Anginosus

This species of streptococcus is a subgroup of the viridans streptococci and are considered normal flora of the oral cavity, GI tract, and vagina. These Gram-Positive Cocci in chains are nonmotile facultative anaerobes that demonstrate an oddity of having variable hemolysis (alpha, beta, or gamma). Lancefield classifications normally classify the members of Streptococcus based on antigens, group properties, and biochemical reactions such as hemolysis, however, the unique thing of this species is they are very variable in the Lancefield antigens and hemolysis patterns and can differ from strain to strain (Al-Charrakh & Alaa 2011).  

The pathogenicity factors of this species are not fully understood and are thought to be a combination of protective capsules, exotoxins, and/or hydrolytic enzymes. Infections range from abscess formation & oral infections to CNS infections and bacteremia. Of all the unique properties these species have, the most clinically relevant is their resistance patterns to antibiotics. Ceftriaxone & vancomycin tend to be the treatments of choice due to their all too common resistance to penicillin, cephalexin, amoxicillin-clavulanic acid, fluoroquinolones, sulfonamides, ampicillin, cefotaxime, cefepime, and tetracyclines (Al-Charrakh & Alaa 2011).

Left untreated, a multitude of complications can arise such as bacteremia, brain and liver abscesses, empyema, or even Lemierre’s Syndrome, which was reported in a case report by Camacho-Cruz J, Preciado H, Beltrán N, Fierro L, & Carrillo J, 2019. 

When to Look Outside the Box

Generally, these types of cases visit Urgent Cares first, get an appropriate empiric antibiotic for the presumed common causes of strep throat and go home, only to come back a few days later with no relief and the disease process has worsened significantly. Usually by the time these cases visit the ED, the lesions are necrotic, systemic symptoms are setting in such as tachycardia, fever, vomiting, and patient looks very uncomfortable to downright ill. The initial tests for the common bugs are your rapid strep test, and PCR DNA tests for strep. The problem with these two tests is that these are highly specific for only one species of strep, Group A Strep, which is the one most providers worry about because there are so many clinically relevant sequalae for an untreated infection. 

If the patient presents after several days of outpatient antibiotics such as cephalexin or Augmentin and seems to have worsened, your patient is showing systemic signs, or looks ill and the rapid strep or PCR DNA tests are both of no help for identification, it is time to think outside the box and get a general culture of the throat or necrotic lesion if present. If patient has risk factors for developing certain infections due to their past medical history or current life choices such as pseudomonas, gonorrhea, etc., don’t forget to add adequate coverage for these organisms. If gonorrhea is on your differential, lets take you back to 2^nd year of medical school when you were learning about microbiology. Neisseria gonorrhoeae is a gram-negative diplococcus that grows on Thayer Martin media, which is chocolate agar and contains vancomycin, colistin, nystatin, and trimethoprim, which inhibits growth of other organisms while promoting growth of N. gonorrhoeae. 

So, remember to reach out to your lab for help if considering a unique organism, as they will always be able to help guide you with the appropriate media/best tests for whatever you are considering. If those systemic signs of infection are present and/or the patient looks ill, it is time to institute broad-spectrum antibiotics such as ceftriaxone and/or vancomycin for adequate coverage of gram-positive, gram-negative, and MRSA coverage if patient has risk factors, and of course follow your institutes sepsis guidelines if meeting criteria. 

Conclusion:

When evaluating a patient with a presumed pharyngitis and response to therapy is underwhelming, consider reevaluation with culture to possibly identify alternative organisms involved so that targeted therapy can be achieved. Other notes to consider are that Strep A PCR is highly sensitive (~96%) & specific (~98%) to only Group A Strep and if considering other groups, a culture of the location of infection should be obtained for delineation of other groups of streptococci or other organisms involved. As a good rule of thumb, broad spectrum antibiotics such as ceftriaxone and vancomycin together supply good coverage for gram-positive, gram-negative, and MRSA related infections while a more targeted approach is sought.  

Authors:
William Hall IV, MD
Peer reviewed and edited by:
Marc Immerman, MD